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T Kohl

Publications and source records attributed to T Kohl.

At least 19 recordsLinked to original sources

Analysis of the stepwise clinical introduction of experimental percutaneous fetoscopic surgical techniques for upcoming minimally invasive fetal cardiac interventions.

BACKGROUND: This study assessed the feasibility and safety of surgical techniques developed in sheep for fetoscopic fetal cardiac interventions during three selected less complex procedures for noncardiac fetal conditions in humans. On the basis of this assessment, the implications for the clinical introduction of minimally invasive fetoscopic fetal cardiac interventions in the near future are discussed. METHODS: The authors performed 16 percutaneous fetoscopic procedures in 13 human fetuses at between 19 + 2 and 34 + 6 weeks of gestation, then analyzed various parameters of surgical relevance for minimally invasive fetoscopic fetal cardiac interventions. Each of the three noncardiac malformations posed typical surgical challenges that will be critical for the technical success of minimally invasive fetoscopic cardiac interventions. RESULTS: Overall technical success was achieved in 14 of the 16 procedures. Percutaneous fetoscopic surgery did not result in any untoward effects and was well tolerated by all but two pregnant women: one with bleeding complication and one with mild postoperative pulmonary edema. No fetal complications or injuries from the various percutaneous fetoscopic surgical approaches were observed. CONCLUSIONS: The author's experience with surgical techniques introduced for percutaneous fetoscopic fetal cardiac intervention in selected noncardiac fetal lesions has led them to believe the time has come for the clinical introduction of fetoscopic fetal cardiac interventions. After an adequate learning curve supervised by committees of human research, the overall outcome and quality of postnatal life for the unborn patients ultimately will determine whether fetoscopic or other fetal cardiac interventions will be better therapeutic alternatives to currently available postnatal procedures.

Female↗

Changing attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care center.

OBJECTIVE: To evaluate attitudes towards non-invasive aneuploidy screening at advanced maternal age in a German tertiary care centre and to compare the rate of invasive testing over a period of four years. METHODS: A retrospective analysis of 2657 singleton pregnancies with targeted first and second trimester ultrasound examination at 11-14, 15-18 and 19-23 weeks' gestation. RESULTS: The number of patients at or beyond 35 years increased by 36 % over this period. Concomitant with an increasing proportion of first trimester examinations (+ 13 %), a decrease in 15-18 weeks' examinations (- 14 %), but no changes regarding the 19-23 weeks' examination were observed. A total of 78 (2.9 %) abnormal karyotypes were found and 92 % (56/61) of the cases with autosomal trisomy had sonographic markers suggestive of foetal aneuploidy. The proportion of diagnosed chromosomal abnormalities at 11-14 weeks increased from 14 % in the first half to 49 % in the second half of the study period (p < 0.01). We observed a significant decrease in the rate of invasive procedures, especially in women reassured by a normal ultrasound examination (54 % versus 37 %, p < 0.01). CONCLUSION: There is an increasing acceptance of first trimester targeted ultrasound examination with the potential advantage of an earlier diagnosis of foetal aneuploidy. Furthermore, we observed annually increasing numbers of women who used the results of the ultrasound examination to guide their final decision about invasive testing, rather than undergo genetic testing as a primary option.

Aneuploidy↗

Fetoscopic and ultrasound-guided decompression of the fetal trachea in a human fetus with Fraser syndrome and congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia.

Congenital high airway obstruction syndrome (CHAOS) from laryngeal atresia bears a poor prognosis for hydropic fetuses owing to cardiac failure. We attempted percutaneous fetoscopic and ultrasound-guided tracheal decompression in a hydropic human fetus with CHAOS associated with Fraser syndrome. Percutaneous fetoscopic and ultrasound-guided tracheal decompression was performed using three trocars under general materno-fetal anesthesia at 19 + 5 weeks of gestation. Abnormal fetoplacental blood flow normalized within hours as a result of the intervention. Furthermore, a normalization of lung : heart size and lung echogenicity was observed within days. Resolution of hydrops was complete within 3 weeks. Premature rupture of membranes and premature contractions prompted emergency delivery of the fetus by ex-utero intrapartum treatment (EXIT) at 28 + 2 weeks of gestation. Following delivery, the lungs could be ventilated at low pressures and ambient oxygen concentration. Weaning from ventilation was achieved at 18 days of postnatal life. Our experience indicated that percutaneous fetoscopic and ultrasound-guided decompression of the fetal trachea is feasible and may permit normalization of hemodynamics in hydropic human fetuses with CHAOS from laryngeal atresia. The procedure may also result in normalization of heart : lung size and provide the time needed to regain the function of the overstretched diaphragm in this grave fetal condition.

Airway Obstruction↗

Prenatal diagnosis of persistent left superior vena cava and its associated congenital anomalies.

OBJECTIVE: To evaluate the associated conditions and the outcome of persistent left superior vena cava (PLSVC) detected in fetal life. METHODS: This was a retrospective review of all cases of PLSVC detected prenatally between 1998 and 2004 in two tertiary referral centers in Germany. Patient charts, ultrasound video recordings and still frames of all cases were reviewed for associated conditions and outcome. RESULTS: Eighty-two cases of PLSVC were detected in the study period. Thirty-seven cases (45%) were associated with heterotaxy syndromes, 19 (23%) with isolated cardiac malformations, seven (9%) with aneuploidy, six (7%) with complex malformation syndromes and six (7%) with isolated extracardiac malformations. Seven cases (9%) had no associated condition. Eighty-three percent of the fetuses in this series had associated cardiac malformations; the most frequent cardiac malformations in those with heterotaxy syndromes were complete atrioventricular septal defect (75%) and right outflow tract obstruction (58%). After exclusion of cases with heterotaxy, most congenital heart defects were ventricular septal defects (41%) and coarctation (34%). The outcome of PLSVC was determined solely by the associated conditions. After exclusion of terminated cases, heterotaxy syndromes as well as complete atrioventricular septal defects were associated significantly with perinatal and infant death. In contrast, all cases with isolated PLSVC or associated correctable extracardiac malformations survived and were doing well at the time of writing. CONCLUSIONS: PLSVC detected in fetal life has to be followed by a meticulous inspection of the fetal anatomy as it is frequently associated with heterotaxy syndromes, other cardiac/non-cardiac malformations and aneuploidy that determine the outcome. Isolated PLSVC is a benign vascular anomaly and may not affect the outcome.

Chromosome Aberrations↗

Ductus venosus blood flow alterations in fetuses with obstructive lesions of the right heart.

OBJECTIVE: To assess the impact of isolated lesions of the fetal right heart on ductus venosus (DV) blood flow profiles. METHODS: Retrospective evaluation of DV blood flow profiles in 83 fetuses with isolated right-sided cardiac lesions. Cases were divided into two groups. Group A had right-sided cardiac lesions associated with a large ventricular septal defect that equalized interventricular pressures (double outlet right ventricle (n = 12), tetralogy of Fallot (n = 19), pulmonary atresia (n = 5)). Group B had right-sided cardiac lesions with obstruction of the inflow (tricuspid atresia with ventricular septal defect (n = 14)) or obstruction of the outflow with intact ventricular septum (Ebstein's anomaly (n = 13), pulmonary stenosis (n = 13) and pulmonary atresia (n = 7)). Comparisons were made with 585 uneventful singleton pregnancies and previously published normative values. RESULTS: Fetuses in Group B had significantly higher rates of abnormal DV flow profiles compared to Group A and controls (P < 0.01). Conversely, there were no significant differences concerning DV parameters between fetuses in Group A and controls. Despite these different DV flow characteristics, there were no significant differences concerning signs of cardiac failure and/or survival to the perinatal period between the two groups. CONCLUSIONS: Right-sided cardiac lesions with obstruction of the inflow or outflow with intact ventricular septum are significantly associated with abnormally high pulsatilities in the DV and may even cause a reversal of flow during atrial contraction. These changes do not necessarily indicate cardiac failure, as they are primarily attributable to the special hemodynamics of the cardiac defect.

Analysis of Variance↗

Absence of ductus venosus-importance of umbilical venous drainage site.

OBJECTIVE: To evaluate the conditions associated with absent ductus venosus (ADV) diagnosed by prenatal ultrasonography. METHODS: Retrospective review of 23 cases with ADV diagnosed in two tertiary referral centers with a general screening policy concerning Doppler assessment of the ductus venosus. The results are discussed together with 63 cases from a review of the literature. RESULTS: In 19 fetuses the umbilical vein connected to the portal sinus, while the remaining four fetuses had extrahepatic umbilical venous drainage. Associated anomalies were present in 15 out of 23 fetuses: complex malformation syndromes (n = 6), chromosomal anomalies (n = 4), isolated cardiac defects (n = 4) and isolated extracardiac anomalies (n = 1). Eight fetuses had either no associated anomalies or minor anomalies. Hydropic changes were present in 12 of the 23 fetuses. In common with the reviewed cases, the presence of cardiac malformations, complex non-chromosomal malformation syndromes and hydrops was significantly associated with intrauterine or postnatal death while the type of umbilical venous drainage was not significantly different between survivors and non-survivors. However, among fetuses with no or minor associated anomalies the outcome was significantly better in the group without liver bypass. CONCLUSIONS: ADV is significantly associated with fetal cardiac and extracardiac anomalies, aneuploidies and hydrops. Fetuses with liver bypass have an additional risk of developing congestive heart failure that significantly affects outcome, even if the fetal cardiovascular anatomy is otherwise normal. ADV without liver bypass seems to have a more favorable prognosis if it is not associated with other malformations.

Aneuploidy↗

Plant-produced cottontail rabbit papillomavirus L1 protein protects against tumor challenge: a proof-of-concept study.

The native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically via Agrobacterium tumefaciens transformation and transiently via a tobacco mosaic virus (TMV) vector in Nicotiana spp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.

Agrobacterium tumefaciens↗

Atrioventricular block detected in fetal life: associated anomalies and potential prognostic markers.

OBJECTIVES: To assess the spectrum of anomalies associated with fetal heart block and to identify possible prognostic markers. METHODS: Retrospective review of all cases of second- or third-degree heart block identified in two tertiary referral centers in Germany (Bonn and Lübeck) and one in the USA (Baltimore). RESULTS: Sixty fetuses with heart block were identified in the study period. Thirty-two had complex cardiac malformations, 31 of them associated with left isomerism. The outcomes of these fetuses were 22 terminations of pregnancy (TOP), three intrauterine fetal deaths (IUFD), three neonatal deaths (NND), two childhood deaths (CD) and there were two survivors. In 20 cases without complex cardiac malformations maternal antinuclear-antibodies were detected. Their outcomes were 2 TOP, 1 IUFD, 1 NND and 16 survived. The remaining eight cases had neither complex cardiac malformations nor associated maternal antibodies. Their outcomes were 1 TOP, 2 IUFD, 2 NND and 3 survived. After exclusion of terminated cases, hydrops as well as the presence of cardiac defects was significantly associated with non-survival (P < 0.01). The cardiothoracic circumference ratio was significantly higher in hydropic fetuses and significantly negatively correlated with survival in immune-mediated cases (P < 0.01). Atrial and ventricular frequencies and their evolution did not accurately predict fetal or neonatal outcome. Sympathomimetic treatment in seven cases was not associated with favorable fetal outcome in cases of hydrops or cardiac malformations. CONCLUSIONS: The most important marker predicting adverse outcome in cases of heart block is fetal hydrops, followed by the association with complex cardiac malformations. Cases without cardiac malformations have a significantly better prognosis, especially in the absence of severe cardiomegaly.

Adult↗

Fetal echocardiographic evaluation of atrial morphology and the prediction of laterality in cases of heterotaxy syndromes.

OBJECTIVE: To evaluate whether abnormal atrial morphology, which is well recognized in autopsy series, is detectable by fetal echocardiographic examination of the four-chamber view, and can therefore be utilized to differentiate left from right isomerism in heterotaxy syndromes. METHODS: This study was a retrospective review of 30 cases with prenatally diagnosed heterotaxy syndromes. Ultrasound video recordings and still images were reviewed with respect to atrial morphology in the four-chamber view. In 25 cases the morphology of both atria was sufficiently well visualized on the recordings to be evaluated and only these were included in the study. RESULTS: Two types of atrial morphology were distinguished in our cohort: a sickle-shape with the tip pointing laterally and apically, and a blunt shape resembling the usual atrial appearance in the four-chamber view. Nineteen out of the 25 cases (76%) presented with isomerism of the atria in the four-chamber view. Thirteen had bilateral sickle-shaped atrial morphology, all associated with left isomerism. Six had bilateral blunt-shaped atrial morphology, all associated with right isomerism. The atria of the remaining six cases were not isomeric, the right atrium being sickle-shaped and the left blunt-shaped. Five of the latter cases were associated with left and one with right isomerism. CONCLUSIONS: The majority of prenatally diagnosed heterotaxy syndromes seem to present with isomeric atrial morphology in the four-chamber view. In these cases a differentiation between left and right isomerism can be based on the two distinct types of atrial morphology. This may further enhance the prenatal differentiation of these syndromes.

Chi-Square Distribution↗

Atypical ductus venosus blood flow pattern in fetuses with severe tricuspid valve regurgitation.

We observed seven cases of atypical ductus venosus (DV) blood flow velocity waveform pattern with impairment of systolic forward flow resulting in a notch or a significant reduction in peak velocity during the S-wave in systole. All affected fetuses had severe tricuspid valve regurgitation associated with congestive heart failure and/or cardiac malformations. The decrease in venous systolic forward flow modulates the venous pulsatility indices towards more favorable values and should be considered when fetuses with tricuspid regurgitation are followed by Doppler assessment of the DV. Detection of these changes in the DV flow profile should prompt detailed color Doppler echocardiography with special emphasis on right atrioventricular valve regurgitation.

Blood Flow Velocity↗

Fetal transesophageal echocardiography: clinical introduction as a monitoring tool during cardiac intervention in a human fetus.

Because of insufficient imaging by maternal transabdominal fetal echocardiography (TAE) in a human fetus with aortic atresia, imperforate atrial septum and progressive cardiac failure, we assessed the feasibility of fetal transesophageal echocardiography (TEE) as a monitoring tool during fetal cardiac intervention at 24 + 6 weeks of gestation. Percutaneous fetoscopic intraesophageal deployment of the ultrasound catheter was achieved and did not result in any maternal or fetal complications. Fetal TEE permitted substantially clearer definition of fetal cardiac anatomy and intracardiac device manipulations than conventional maternal TAE. Despite the employment of various devices, no sufficiently large opening could be achieved within the atrial septum. Although the fetus tolerated the procedure remarkably well and satisfactory fetoplacental flow could be documented at the end of the procedure, the fetus died from progressive cardiac failure 3 days after the intervention. Fetoscopic TEE is feasible in the human fetus and permits substantially clearer definition of fetal cardiac anatomy and intracardiac manipulations than conventional maternal TAE. Based on the observation of spontaneous closure of multiple iatrogenic perforations of the atrial septum, specialized devices are required in order to improve the technical success rate of septoplasty methods and hence the survival odds of these high-risk patients.

Adult↗

Percutaneous fetoscopic tracheal balloon occlusion in sheep.

BACKGROUND: In order to minimize maternal trauma from current techniques for temporary fetoscopic tracheal occlusion, we tried to develop a percutaneous fetoscopic technique in sheep. METHODS: In nine ewes between 77 and 128 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was positioned and the feasibility of fetal laryngoscopy and percutaneous fetoscopic tracheal balloon occlusion was assessed. RESULTS: Percutaneous intraamniotic access, fetal positioning, oropharyngeal sheath insertion, and fetoscopic laryngoscopy were achieved in all nine fetal sheep. Following some technical modifications to the working channel of the fetoscope, percutaneous fetoscopic tracheal balloon occlusion was successfully achieved in the last seven sheep. CONCLUSION: Percutaneous fetoscopic balloon occlusion of the fetal trachea can effectively and safely be achieved in sheep. Because intraamniotic spatial relationships, fetal position, and umbilical cord length are technically less favorable in sheep, our operative techniques might be feasible in humans even if difficult intraamniotic conditions are encountered.

Animals↗

Percutaneous fetoscopic patch coverage of experimental lumbosacral full-thickness skin lesions in sheep.

BACKGROUND: In order to minimize maternal trauma from open fetal surgery for prenatal coverage of fetal myelomeningoceles in humans, we assessed the feasibility of a percutaneous fetoscopic approach in sheep. METHODS: In seven ewes between 90 and 100 days of gestation, the amniotic cavity was entered percutaneously. Each fetus was postured and a full-thickness skin lesion was created in the lumbosacral region. Then, the feasibility of covering this lesion with a patch and fetal skin by standard endoscopic suturing techniques (n = 3) or robot assistance (n = 4) was assessed. RESULTS: Percutaneous fetoscopic patch and skin coverage of the full-thickness skin lesion was achieved in six of the seven fetal sheep. Five fetuses survived gestation and were delivered healthy. CONCLUSIONS: Percutaneous fetoscopic posturing and patch coverage of lumbosacral full-thickness skin lesions can effectively and safely be achieved in sheep. This approach promises to provide a substantial reduction of maternal trauma from fetal surgery for myelomeningoceles.

Animals↗

Prenatal diagnosis of cardiosplenic syndromes: a 10-year experience.

OBJECTIVE: To assess the accuracy of fetal echocardiography in the prenatal diagnosis of cardiosplenic syndromes and the spectrum of associated anomalies. METHODS: This was a retrospective survey of fetuses in our databases over a period of 10 years with postnatally confirmed prenatal diagnosis of cardiosplenic syndromes. RESULTS: In 32 of 35 fetuses the prenatal diagnosis of cardiosplenic syndromes was confirmed postpartum. Twenty-two fetuses had left isomerism. Their main prenatal ultrasound features were interrupted inferior vena cava (n = 21), complete atrioventricular septal defect (n = 15), viscerocardiac heterotaxy (n = 15), persistent bradyarrhythmia (n = 12) and fetal hydrops or nuchal edema (n = 12). Twelve pregnancies were terminated, two fetuses were stillborn and eight infants survived. Ten fetuses had right isomerism. Their main sonographic features were juxtaposition of the descending aorta and inferior vena cava (n = 7), complete atrioventricular septal defect (n = 7), left persistent superior vena cava (n = 6) and viscerocardiac heterotaxy (n = 6). In this group there was one stillbirth, five infant deaths and four survivors. The overall survival rate and spectrum of other cardiac malformations were similar between the two groups. Prenatal diagnosis of other visceral features of cardiosplenic syndromes was inconsistent. CONCLUSION: Cardiosplenic syndromes can be diagnosed with high accuracy by prenatal sonography. A diagnosis of left isomerism should be strongly suggested in the presence of a combination of at least two of the following: (1) complete atrioventricular septal defect or other structural heart disease; (2) interruption of inferior vena cava with azygos continuation; (3) early fetal heart block; (4) viscerocardiac heterotaxy. Right isomerism should be suspected in the presence of a combination of at least two of the following: (1) structural heart disease, namely complete atrioventricular septal defect; (2) juxtaposition of inferior vena cava and descending aorta; (3) viscerocardiac heterotaxy.

Echocardiography↗

Review of diagnosis, treatment, and outcome of fetal atrial flutter compared with supraventricular tachycardia.

OBJECTIVE: To review the diagnosis, treatment, and outcome of fetal atrial flutter compared with supraventricular tachycardia. DESIGN: Retrospective review of published reports: 11 papers about fetal tachyarrhythmia published between 1991 and 2002 were selected for review. MAIN OUTCOME MEASURES: All selected studies were analysed for the type of arrhythmia, degree of atrioventricular block in atrial flutter, occurrence of hydrops fetalis, gestational age at diagnosis, first and second line drug treatment, associated cardiac and extracardiac malformations, and mortality of the fetuses. RESULTS: Atrial flutter accounted for 26.2% of all cases of fetal tachyarrhythmias, and supraventricular tachycardia for 73.2%. Hydrops fetalis was reported in 38.6% and 40.5% of fetuses with atrial flutter and supraventricular tachycardia, respectively (NS). Hydropic fetuses with atrial flutter had higher ventricular rates (median 240 beats/min, range 240-300) than non-hydropic fetuses (220 beats/min, range 200-310) (p = 0.02), whereas the atrial rates were not significantly different (median 450 beats/min, range 370-500). Digoxin treatment resulted in a higher conversion rate in non-hydropic fetuses with fetal tachyarrhythmias than in hydropic fetuses (p < 0.001). The overall mortality of atrial flutter was similar to that of supraventricular tachycardia, at 8.0% v 8.9% (p = 0.7). CONCLUSIONS: The prevalence of hydrops fetalis did not differ in fetal atrial flutter and supraventricular tachycardia with 1:1 conduction. There was no difference between the response rate to digoxin in fetus with atrial flutter or supraventricular tachycardia. Mortality was similar in the two types of tachyarrhythmia.

Anti-Arrhythmia Agents↗

Comparison of ductus venosus blood flow waveform indices of 607 singletons with 133 multiples at 10-14 weeks gestation. An evaluation in uncomplicated pregnancies.

Abnormal flow profiles in the ductus venosus during early pregnancy may aid in diagnosing chromosomopathies, malformations, congenital heart disease, and twin-twin transfusion syndrome in monochorionic twins. Whereas reference values of ductus venosus flow velocities and waveform indices for the late first and early second trimester have been reported in singletons, similar reference values for multiple pregnancies have not been established in this age group. Therefore, the aim of the present ultrasound study in 119 multichorionic and 14 monochorionic multiples in human fetuses between 10-14 weeks of gestation was to establish reference values for ductus venosus flow waveform indices for multiple pregnancies. Data in multiples were compared with those of 607 singletons. Analysis of the ductus venosus (DV) flow velocity waveforms consisted of the calculation of the pulsatility index (PIV) and peak velocity index (PVIV) for veins. Comparing the data of singletons and multichorionic multiples, no statistically significant differences were observed between the two groups in any of the assessed Doppler parameters. The DV Doppler parameters of the 14 monochorionic twins that were analysed separately in order to avoid any potential bias from preclinical twin-twin transfusion syndrome were also found within the normal ranges. In the study population fetal heart rate did neither significantly correlate with PIV nor with PVIV. PIV and PVIV decreased from 10 to 14 weeks gestation. A 2.9% rate of absent or reverse flow during atrial contraction in normal fetuses at 10-14 weeks gestation was found and needs to be taken into consideration when this pattern is defined abnormal in screening tests for fetal chromosomopathies or congenital heart disease.

Blood Flow Velocity↗